Succinate has many industrial uses. As a specialty chemical, it is a flavor and formulating ingredient in food processing, a pharmaceutical ingredient, and a surfactant. Succinate's greatest market potential, though, would be its use as an intermediary commodity chemical feedstock for producing bulk chemicals, stronger-than-steel plastics, ethylene diamine disuccinate (a biodegradable chelator), and diethyl succinate (a green solvent for replacement of methylene chloride). Along with succinic acid, other 4-carbon dicarboxylic acids from the Krebs Cycle, such as malic acid and fumaric acid, also have feedstock potential.
More than 17,000 tons of succinate are sold per year. It is currently sold in the U.S. for $2.70-4.00/lb, depending on its purity. Succinate is currently produced petrochemically from butane through maleic anhydride. It can also be made by fermentation from glucose at a production cost of about $1.00/lb, but for succinate to be competitive with maleic anhydride as a commodity chemical, its overall production cost should be lowered to approximately 15 cents/lb.
The production of succinate, malate, and fumarate from glucose, xylose, sorbitol, and other “green” renewable feedstocks (in this case through fermentation processes) is a way to supplant the more energy intensive methods of deriving such acids from nonrenewable sources.
Succinate is an intermediate for anaerobic fermentations by propionate producing bacteria (e.g., Actinobacillus succinogenes), but those processes result in low yields and concentrations and these bacteria are generally not cost effective to use.
It has long been known that mixtures of acids are produced from E. coli fermentation. However, for each mole of glucose fermented, only 1.2 moles of formic acid, 0.1-0.2 moles of lactic acid, and 0.3-0.4 moles of succinic acid are produced. As such, efforts to produce carboxylic acids fermentatively have resulted in relatively large amounts of growth substrates, such as glucose, not being converted to desired product, and this greatly reduces the cost effectiveness of the method.
Metabolic engineering has the potential to considerably improve bacterial productivity by manipulating the throughput of metabolic pathways. Specifically, manipulating enzyme levels through the amplification, addition, or deletion of a particular pathway can result in high yields of a desired product. Several examples of increasing succinate levels through metabolic engineering are known, including several patented examples from our own group. However, there is always room for continued improvement.
What is needed in the art is an improved bacterial strain that produces higher levels of succinate and other carboxylic acids than heretofor provided.